Secondaryalkoxy-1-alkenes have utility as intermediates in the preparation of pharmaceutical compounds. Methods for the preparation of alkoxy alkenes, have been reported in the prior art. However, none of them provides a general procedure for the preparation of secondaryalkoxy-1-alkenes from cyclic and acyclic ketones. The methods disclosed are limited to the production of primaryalkoxy alkenes and teach the acid-catalyzed elimination of a primary alcohol group from a dialkyl ketal.
As used herein, ketal means a cyclic or acyclic ketone that is subjected to a reaction with an alcohol to form a 1,1-dialkoxyalkane, the latter also referred to as ketone acetals. This definition is more specific, and is to be distinguished from terminology employed in the technical literature where ketal and acetal are sometimes used interchangeably. Thus, a ketone R'R"C.dbd.O is thus reacted with 2 R'"--OH to produce the ketal R'R"C(OR'").sub.2 and water.
Several researchers have reported on reaction systems that included the formation of secondaryalkoxy-1-alkenes. Roelofsen et al. disclose a reaction scheme for producing de-sec-alkyl ketals and reported the observation of an equilibrium side reaction in which a secondaryalkoxy-1-cyclohexene was produced as an undesired by-product. Synthesis, August 1972, pp. 419-420.
Howard et al. in an article entitled "Ketals of Monohydric Secondary Alcohols", Journal of Organic Chemistry, April 1960, pp. 525-30, describe at p. 526, first column, work by Reichle who reportedly obtained diisopropyl ketals from cyclic ketones and triisopropyl orthoformate. MacKenzie et al. reported the formation of a primaryalkoxy alkene during the transformation of cyclohexanone into its diethyl ketal using triethyl orthoformate as a reactant. However, repeating this reaction scheme employing sec-tributyl orthoformate in place of triethyl orthoformate failed to produce a secondaryalkoxy cycloalkene. Gassman et al. reported a general method to synthesize alkoxy alkenes (enol ethers) from ketals/acetals, which involved treatment of an appropriate ketal/acetal with a 10-75% molar excess of trimethylsilyl triflate and a 20-90% molar excess of N,N-diisopropylcthylamine.
Katritzky et al. reported a method for the preparation of ketone enol ethers with both primary and secondaryalkoxy groups. However, the process disclosed requires the intermediate preparation of a benzotriazoyl derivative and a laborious work-up resulting in the generation of a large quantity of undesirable by-products that must be disposed of with the expenditure of additional time and resources.
It is also known from U.S. Pat. No. 5,401,885 to prepare dialkoxycycloalkanes by reacting a cycloalkanone, an iminoether hydrochloride and a secondary alkanol.
It is therefore an object of this invention to provide as a general synthesis, a one-step method to convert cyclic and acyclic ketones into their corresponding secondaryalkoxy-1-alkenes.
It is another object of this invention to provide a process that can produce commercial quantities of alkoxy-1-alkenes economically and with a minimum of undesirable by-products.